title: Determination of Mycophenolic acid in the vitreous humor using the HPLC-ESI-MS/MS method: application of intraocular pharmacokinetics study in rabbit eyes with ophthalmic implantable device.
abstract: Mycophenolic acid (MPA) is an immunosuppressive agent widely used in the treatment of solid organ transplant rejection. The success of MPA in the treatment of inflammatory intraocular diseases has been reported in recent literature. The treatment of inflammatory eye diseases in the posterior chamber is a challenge due to the anatomy of the eye, which presents certain barriers to drug access. Thus, the bioavailability of drugs in the eye is quite low, and successful drug delivery may well represent a key limiting factor to attaining a successful therapeutic strategy. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions. Thus, a novel delivery system based on a biodegradable polymeric device, which can be implanted inside the eye and deliver MPA directly to the target, is being developed. Specific analytical methods to determine the use of effective drugs within the eye are needed to characterize this device. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantitation of MPA in the vitreous humor of rabbits was developed and validated. The vitreous was collected from rabbits, extracted by a protein precipitation extraction procedure and then separated on a C18 column with a mobile phase comprised of 0.15% aqueous acetic acid and methanol (60:40, v/v). The calibration curve was constructed within the range of 3-10,000 ng/mL for MPA. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the MPA concentration in the vitreous humor of rabbits treated with an ocular implantable device.
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil. ricardobyrro@bol.com.br
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martins Duarte Byrro
authors.forename: Gustavo
authors.initials: G
authors.lastname: de Oliveira Fulgêncio
authors.forename: Paula
authors.initials: P
authors.lastname: Rocha Chellini
authors.forename: Armando
authors.initials: A
authors.lastname: da Silva Cunha
authors.forename: Gerson Antônio
authors.initials: GA
authors.lastname: Pianetti
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000493:pharmacokinetics; D009173:Mycophenolic Acid / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014822:Vitreous Body / Q000737:chemistry / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Controlled release; HPLC–ESI-MS/MS; Mycophenolic acid; Ophthalmic drug delivery; Vitreo drug definition